Effect of the V3 loop deletion of envelope glycoprotein on cellular responses and protection against challenge with recombinant vaccinia virus expressing gp160 of primary human immunodeficiency virus type 1 isolates
Effect of the V3 loop deletion of envelope glycoprotein on cellular responses and protection against challenge with recombinant vaccinia virus expressing gp160 of primary human immunodeficiency virus type 1 isolates
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DOI：
10.1128/jvi.76.9.4222-4232.2002
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发表时间：
2002-05-01
影响因子：
5.4
通讯作者：
Kozbor, D
中科院分区：
文献类型：
--
作者：
Kiszka, I;Kmieciak, D;Kozbor, D
在 HLA-A2/K-b 转基因小鼠中评估了 1 型人类免疫缺陷病毒 (HIV-1) 包膜蛋白 (DeltaV3) 诱导的细胞毒性 T 淋巴细胞 (CTL) 反应的强度和广度，其中超变 V3 环已被删除 (DeltaV3)。结果表明，表达 HIV-1(IIIB) 或 HIV-1(89.6) 包膜糖蛋白 DeltaV3 突变体的疫苗比野生型 (WT) 疫苗诱导更广泛的 CD8(+) T 细胞活性。具体而言，这些差异与对包膜糖蛋白的保守HLA-A2限制性CTL表位的较高反应相关，并且可能与表达DeltaV3突变体的靶细胞中表位-HLA-A2复合物增加的细胞表面占据相关。在小鼠攻击系统中使用表达原代 HIV-1 分离株异源 gp160 的重组牛痘病毒，我们观察到用 DeltaV3 免疫的动物对病毒传播的抵抗程度高于 WT 包膜疫苗。这种保护作用与包膜特异性CD8+T细胞的存在有关，因为在攻击时通过抗CD8抗体处理消除这些细胞会消除疫苗诱导的保护作用。我们的研究结果为增强包膜特异性 CTL 反应广度的方法提供了见解。
The magnitude and breadth of cytotoxic-T-lymphocyte (CTL) responses induced by human immunodeficiency virus type 1 (HIV-1) envelope protein from which the hypervariable V3 loop had been deleted (DeltaV3) were evaluated in the HLA-A2/K-b transgenic mice. It was demonstrated that vaccines expressing the DeltaV3 mutant of either HIV-1(IIIB) or HIV-1(89.6) envelope glycoprotein induced broader CD8(+) T-cell activities than those elicited by the wild-type (WT) counterparts. Specifically, the differences were associated with higher responses to conserved HLA-A2-restricted CTL epitopes of the envelope glycoprotein and could be correlated with an increased cell surface occupancy by the epitope-HLA-A2 complexes in target cells expressing the DeltaV3 mutant. Using recombinant vaccinia virus expressing heterologous gp160 of primary HIV-1 isolates in a murine challenge system, we observed that the extent of resistance to viral transmission was higher in animals immunized with the DeltaV3 than the WT envelope vaccine. The protection was linked to the presence of envelope-specific CD8(+) T cells, since depletion of these cells by anti-CD8 antibody treatment at the time of challenge abolished the vaccine-induced protection. The results from our studies provide insights into approaches for boosting the breadth of envelope-specific CTL responses.